A recent prospective study of post transfusion hepatitis conducted by us has documented not only an inordinate frequency of hepatitis (43%) but a high frequency of chronic sequelae of acute hepatitis (40%) following blood transfusions. The objectives of this program are to prospectively follow a group of previously well characterized patients with post transfusion hepatitis to assess the hazards, if any, of simultaneous transfusion of Hepatitis B antigen (HBsAg) and its antibody and to establish the frequency and natural course of the chronic sequelae of acute hepatitis. It will be an objective of these studies to determine if chronic liver disease is more commonly associated with HBsAg positive or negative blood transfusions and to further determine if any specific HBsAg subtypes more commonly result in chronic liver disease. Pilot tubes from all units of blood transfused at the UCLA Center for the Health Sciences have been coded and frozen for the past 2 years. Two weeks after transfusion, pilot tubes initially negative for HBsAg by counterelectrophoresis were rescreened by radioimmunoassay and red cell agglutination. The recipients of HBsAg positive blood units were identified and were followed at 2 week intervals with SGPT and HBsAg levels for 9 months. Each recipient of HBsAg was matched with a recipient of the same race, age and sex who had received the same number of negative blood units. It was of interest to note that of the 9 patients found to have chronic active hepatitis in 1975, four of whom have been biopsied in 1976, 3 have had no progression of their illness while one has had his biopsy revert to a picture of chronic persistent hepatitis. Moreover, of the 4 patients found to have chronic unresolved hepatitis in 1975, 3 of whom have undergone liver biopsy, 1 has had no progression of his disease while 2 now have the histologic picture of chronic persistent hepatitis. Expansion of these studies may enable a clearer definition of the natural course of untreated chronic active hepatitis, chronic unresolved hepatitis and chronic persistent hepatitis and may also reveal with what frequency these liver biopsy pictures change during a period of prospective followup.